title: Structure of the JmjC-domain-containing protein JMJD5.
abstract: The post-translational modification of histone tails is the principal process controlling epigenetic regulation in eukaryotes. The lysine methylation of histones is dynamically regulated by two distinct classes of enzymes: methyltransferases and demethylases. JMJD5, which plays an important role in cell-cycle progression, circadian rhythms and embryonic cell proliferation, has been shown to be a JmjC-domain-containing histone demethylase with enzymatic activity towards H3K36me2. Here, the crystal structure of human JMJD5 lacking the N-terminal 175 amino-acid residues is reported. The structure showed that the Gln275, Trp310 and Trp414 side chains might block the insertion of methylated lysine into the active centre of JMJD5, suppressing the histone demethylase activity of the truncated JMJD5 construct. A comparison of the structure of JMJD5 with that of FIH, a well characterized protein hydroxylase, revealed that human JMJD5 might function as a protein hydroxylase. The interaction between JMJD5 and the core histone octamer proteins indicated that the histone proteins could be potential substrates for JMJD5.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, People's Republic of China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.forename: Chengliang
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Tao
authors.forename: Nini
authors.initials: N
authors.lastname: Chen
authors.forename: Jianye
authors.initials: J
authors.lastname: Zang
mesh_terms: D018360:Crystallography, X-Ray; D019175:DNA Methylation / Q000235:genetics; D056466:Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006657:Histones / Q000737:chemistry / Q000235:genetics; D006801:Humans; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D006657:Histones; D011994:Recombinant Proteins; D012097:Repressor Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D056466:Histone Demethylases; C550342:KDM8 protein, human
keywords: JMJD5; histone demethylases; hydroxylases